Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much ac ....Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much acclaimed and novel pathway that allows efficient, combined cytokine secretion and phagocytosis in macrophages. Our studies proposed here will now expand on this discovery by comparing the phagocytic process, in terms of SNARE-mediated membrane and cytokine trafficking, for a wide range of microbes, highlighting differences that could provide new avenues for drug development. Moreover, since our strategy of using SNAREs to investigate and map trafficking pathways has proven so successful, we will now launch a major large-scale initiative to study ALL SNARE-mediated trafficking pathways in macrophages using a discovery pipeline of assays, including live cell imaging, we have developed. This will provide valuable information on many SNAREs including those associated with disease, and will elucidate trafficking pathways governing all macrophage actions in immunity, including cytokine secretion and antigen presentation. All of these pathways are highly relevant to current drug targets being used clinically or studied in inflammatory disease and for the development of vaccines.Read moreRead less
STudy Of Risk Assessment To Reduce Complications In Patients Following Noncardiac SurgerY (STRATIFY)
Funder
National Health and Medical Research Council
Funding Amount
$436,000.00
Summary
Cardiac problems account for many complications in patients undergoing major non-cardiac surgery, and even apparently minor cardiac damage is a marker of high risk for subsequent adverse events. Unfortunately, while money and effort is expended on identifying patients at risk, the appropriate response to this risk is quite unclear. The performance of bypass surgery or balloon angioplasty in order to treat the underlying coronary disease of at-risk patients is used in other situations, and reduce ....Cardiac problems account for many complications in patients undergoing major non-cardiac surgery, and even apparently minor cardiac damage is a marker of high risk for subsequent adverse events. Unfortunately, while money and effort is expended on identifying patients at risk, the appropriate response to this risk is quite unclear. The performance of bypass surgery or balloon angioplasty in order to treat the underlying coronary disease of at-risk patients is used in other situations, and reduces longterm risk. However, in many patients undergoing major noncardiac surgery, this approach may be inappropriately aggressive, as these patients are often elderly, have other diseases that make heart operations more difficult and risky than usual, and in any case may have a reduced life expectancy from the disease necessitating the operation. As the most critical issue is to ensure that patients undergo their surgery uneventfully, an alternative is the use of intensive medical therapy to protect the heart. This multicentre study, based at Brisbane hospitals that perform large numbers of major operations, will follow up patients for complications, and outcome (including quality of life) will be assessed six months after the operation. We will address two important questions about the efficacy and cost of risk reduction strategies. First, in patients at higher levels of risk and with a positive stress test, could a combination of medical therapy designed to protect the heart be as effective as current approaches, which include the performance of bypass surgery or coronary balloon angioplasty? Second, in patients identified as being at some risk - but low risk - are drugs sufficiently effective to avoid the need for further testing to quantify risk? As the population continues to age, the numbers of at risk patients undergoing major surgery will increase, and answers to these questions will provide important information to guide their management.Read moreRead less
Regulating The Secretion Of Inflammatory Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Cytokines or chemical messengers released by cells are essential for controlling immune responses but, in excess, they cause Crohn's disease and arthritis. Our research aims to block cytokine release as a novel way to ameliorate disease. We have identified specific cellular proteins, called golgins, that can be targeted to reduce cytokines. Here, characterization of golgin mediated cytokine transport in cells and in a mouse disease model is necessary to translate these findings for human benefit
History in their bones: A diachronic, bioarchaeological study of diet, mobility and social organisation from Cambodian skeletal assemblages. Australia will further enhance its role as an innovator in the archaeology of SE Asia through this cross-disciplinary, international collaboration on the mobility, health, age and diet in ancient Cambodia. Local collaborations will be expanded and academic and cultural relations with Cambodia will be reinforced and strengthened. This research will expand ....History in their bones: A diachronic, bioarchaeological study of diet, mobility and social organisation from Cambodian skeletal assemblages. Australia will further enhance its role as an innovator in the archaeology of SE Asia through this cross-disciplinary, international collaboration on the mobility, health, age and diet in ancient Cambodia. Local collaborations will be expanded and academic and cultural relations with Cambodia will be reinforced and strengthened. This research will expand understanding of Cambodian history and underscore its pivotal role in mainland SE Asian archaeology. Australia's advancement of knowledge about Cambodia's rich cultural antiquity will be recognized worldwide by a global community acutely mindful of the losses to culture and heritage endured by Cambodia in the recent past.Read moreRead less
Agriculture and the Late Bronze Age collapse of the Hittite Empire. National benefit will be accrued through the major scholarly contribution the project makes to a key debate in world archaeology, namely the extent to which environmental change affected ancient complex societies, especially climate change. As such it fosters an awareness of world cultures and the interrelation between political stability and environmental change. The project also will encourage international collaboration betwe ....Agriculture and the Late Bronze Age collapse of the Hittite Empire. National benefit will be accrued through the major scholarly contribution the project makes to a key debate in world archaeology, namely the extent to which environmental change affected ancient complex societies, especially climate change. As such it fosters an awareness of world cultures and the interrelation between political stability and environmental change. The project also will encourage international collaboration between Australian, Turkish and Japanese scholars and will provide training for several research scholars in an area of archaeology in which Australia has a recognised major deficit, namely archaeobotany.Read moreRead less
Precisely Dating the Evolution of Complex Societies in Polynesia: The Hawaiian Example. It is of enormous national benefit to develop intellectual innovations that set Australia apart from its neighbours and establish its position as a regional leader in science. Because the Australasian region relies heavily on primary resource exploitation, intellectual developments are crucial for sustainable economic growth. Understanding how societies meet the challenges of resource depletion, landscape de ....Precisely Dating the Evolution of Complex Societies in Polynesia: The Hawaiian Example. It is of enormous national benefit to develop intellectual innovations that set Australia apart from its neighbours and establish its position as a regional leader in science. Because the Australasian region relies heavily on primary resource exploitation, intellectual developments are crucial for sustainable economic growth. Understanding how societies meet the challenges of resource depletion, landscape degradation, drought and population increase can be monitored with archaeological data over hundreds of years. Our research seeks to use an innovative technique for precisely dating major changes in Oceanic societies over the past 500 years, which will provide insights into how modern communities can cope with these problems today. Read moreRead less
Intelligent pattern recognition of water end uses enabling recommendations. This project aims to develop a hybrid machine learning method for autonomously disaggregating high- and low-resolution water flow data received from smart meters into discrete end-use events, and a customised recommender system for efficient resource demand management. Project novelty and significance relates to this coupling and autonomous disaggregation of datasets from advanced sensors, enabling more efficient utility ....Intelligent pattern recognition of water end uses enabling recommendations. This project aims to develop a hybrid machine learning method for autonomously disaggregating high- and low-resolution water flow data received from smart meters into discrete end-use events, and a customised recommender system for efficient resource demand management. Project novelty and significance relates to this coupling and autonomous disaggregation of datasets from advanced sensors, enabling more efficient utility services delivery and lower customer utility bills. Project benefits include enabling utilities to better manage and plan resources in the information age, while empowering customers with real-time water end-use data and behaviour changing consumption recommendations.Read moreRead less
Functional magnetic resonance imaging: Decoding the palimpsest. This project aims to model the dynamics of functional magnetic resonance imaging (fMRI) to image new physiology and attain higher resolution. This will enable new aspects of brain dynamics to be imaged, achieving higher resolution and improving interpretation. This project is expected to improve the use and power of fMRI, unlock new avenues for probing brain function and save experimental costs. This will have many uses in neuroscie ....Functional magnetic resonance imaging: Decoding the palimpsest. This project aims to model the dynamics of functional magnetic resonance imaging (fMRI) to image new physiology and attain higher resolution. This will enable new aspects of brain dynamics to be imaged, achieving higher resolution and improving interpretation. This project is expected to improve the use and power of fMRI, unlock new avenues for probing brain function and save experimental costs. This will have many uses in neuroscience, brain imaging technology and fMRI analysis software.Read moreRead less
Voyaging, Trade and the Development of Ancient Complex Societies in East Polynesia: An Interdisciplinary Approach. Developing a knowledge-based economy has long-term benefits to Australia and is independent of fluctuations in the resource sector on which our nation heavily relies. Intellectual innovations are crucial for sustainable growth and help establish Australia as a regional and world leader in science. We use innovative methods to 'fingerprint' prehistoric stone tools and raw material so ....Voyaging, Trade and the Development of Ancient Complex Societies in East Polynesia: An Interdisciplinary Approach. Developing a knowledge-based economy has long-term benefits to Australia and is independent of fluctuations in the resource sector on which our nation heavily relies. Intellectual innovations are crucial for sustainable growth and help establish Australia as a regional and world leader in science. We use innovative methods to 'fingerprint' prehistoric stone tools and raw material sources for determining the geographic extent of travel between island groups and ascertaining how inter-connected Pacific island communities were about 800 to 200 years ago. Documenting this long-term prehistory will provide insights into our modern neighbours and promote regional understanding, and enhance international collaboration and research training.Read moreRead less